Most cancer drugs are effective in some patients but not others. This results from genetic variation among tumors, and can be observed even among tumors within the same patient. Variable patient response is particularly pronounced with respect to targeted therapeutics. Therefore, the full potential of targeted therapies cannot be realized without suitable biomarkers for determining which patients will benefit from which drugs. The National Institutes of Health (NIH) defines a biomarker as follows:                A characteristic that is objectively measured and evaluated as an indicator or normal biologic or pathogenic processes or pharmacological response to a therapeutic intervention.        
The development of improved diagnostics based on the discovery of biomarkers has the potential to accelerate new drug development by identifying, in advance, those patients most likely to show a clinical response to a given drug. This would significantly reduce the size, length and cost of clinical trials. Technologies such as genomics, proteomics and molecular imaging currently enable rapid, sensitive and reliable detection of specific gene mutations, expression levels of particular genes, and other molecular biomarkers. In spite of the availability of various technologies for molecular characterization of tumors, the clinical utilization of cancer biomarkers remains largely unrealized because few cancer biomarkers have been discovered. For example, a recent review article states:                There is a critical need for expedited development of biomarkers and their use to improve diagnosis and treatment of cancer. (Cho, 2007, Molecular Cancer 6:25)        
Another recent review article on cancer biomarkers contains the following comments:                The challenge is discovering cancer biomarkers. Although there have been clinical successes in targeting molecularly defined subsets of several tumor types—such as chronic myeloid leukemia, gastrointestinal stromal tumor, lung cancer and glioblastoma multiforme—using molecularly targeted agents, the ability to apply such successes in a broader context is severely limited by the lack of an efficient strategy to evaluate targeted agents in patients. The problem mainly lies in the inability to select patients with molecularly defined cancers for clinical trials to evaluate these exciting new drugs. The solution requires biomarkers that reliably identify those patients who are most likely to benefit from a particular agent. (Sawyers, 2008, Nature 452:548-552, at 548)Such comments illustrate the recognition of a need for the discovery of clinically useful biomarkers and diagnostic methods based on such biomarkers.        
Vertebrates, including mammals, have four distinct Notch proteins, also known as Notch receptors (Notch1 to Notch4). All four Notch receptors are type 1 transmembrane proteins that include an extracellular domain, transmembrane domain, and an intracellular domain.
The Notch pathway is a highly conserved system for cell-to-cell signaling. It is present in all metazoans and plays multiple roles in normal growth and development. For a review regarding the Notch pathway, see, e.g., Ilagan et al., 2007, Cell 128:1245-1246. Notch function is complex and highly dependent on cellular context (temporal context, as well as anatomical context). Notch signaling is dysregulated in many cancers. Not only does Notch signaling affect a wide range of cell types and processes, Notch signaling produces opposite effects when activated in different cellular contexts. For example, Notch signaling stimulates proliferation of T cells and inhibits apoptosis, while causing cell cycle arrest and inducing apoptosis in B cells. Notch functions as an oncogene in some cellular contexts, while functioning as a tumor repressor in other cellular contexts.
Notch is a potential therapeutic target in the treatment of certain cancers. However, the complexity of Notch biology makes the effect of Notch pathway inhibition in any given tumor unpredictable. This underscores the need for discovery of a diagnostic method for identifying tumors that will respond to treatment with inhibitors of Notch signaling.